Neuromuscular Disorders

Basic Physiology

• Motor unit comprised of the anterior horn cell in the spinal cord, the motor nerve with its myelin sheath, the termination of the motor nerve at the neuromuscular junction, and the ennervated muscle

•  Any disruption in the motor unit can lead to weakness and impaired reflexes 

• The various acute neuromuscular disease states encountered in the PICU can be differentiated based on history, clinical presentation, physical exam, and clinical course.

Guillain-Barre' Syndrome

• Most common acute NM disorder seen in the PICU

• Various forms with different areas of immune mediated attack : Most common acute inflammatory demyelinating polyneuropathy (AIDP). Others include: Acute motor axonal neuropathy (AMAN) and Miller Fisher syndrome (MFS)

• Ascending paralysis, generally symmetrical

• Prodromal respiratory or gastrointestinal illness (ie campylobacter, CMV)

• Hypo/Areflexia

• Mild sensory symptoms

• Autonomic instability (ie cardiac arrhythmias)

• CSF: Cytoalbuminologic dissociation (nl WBC, high protein after 1st week of symptoms)

• Nerve conduction studies: demyelination, conduction block, temporal dispersion

• Tx: IVIG and plasmpaheresis equally efficacious. Using the two sequentially not better than using one alone

• Fewer relapses if IVIG dose given as 2 g/kg divided over 5 days rather than 2 days (Korinthenberg, Pediatrics 2005)

• Steroids NOT helpful

• Intubation and mechanical ventilation as needed (~25%) (ie if NIF less than about -20 to -25 or FVC < 10-15 cc/kg)

• Miller-Fisher variant: ataxia, areflexia, ophthalmoparesis (bulbar symptoms), linked to Ab against ganglioside GQ1b

Myasthenia Gravis

• Due to antibodies directed at the Achetylcholine receptor (AchR) at the postsynaptic neuromuscular junction

• Presenting symptoms include: ptosis, diplopia, and generalized weakness

• Increasing fatigability

• Classic diagnostic test: Edrophonium (Tensilon) challenge. Edrophonium (short acting anticholinesterase) increases Ach levels at the neuromuscular junction and should lead to transient improvement in symptoms. Must have atropine available to counteract muscarinic cholinergic effects (bradycardia, bronchial secretions/bronchospasm)

• Decremental muscle action potential seen on repetitive nerve stimulation

• Tx with anticholinesterase medications, typically pyridostigmine

• Immunosupressive medications may be used (prednisone, azathioprine, cyclophosphamide, tacrolimus)

• Some also consider thymectomy (moreso in adults and older children)

• Myasthenic crisis (acute worsening of weakness and bulbar symptoms) often requires mechanical ventilation or BiPAP

• Tx for myasthenic crisis includes IVIG, plasmpaheresis

• Steroids, aminoglycosides, and NMB can exacerbate weakness

• Autoimmune disease seen in ~15% of patients with juvenile MG

Tick Paralysis

• Neurotoxin inhibits release of acetylcholine at the presynaptic terminal, causing acute flaccid paralysis

• Fatigue, irritability, pain, cerebellar signs, ataxia

• Symmetrical ascending flaccid paralysis. Can be mistaken for GBS

• No systemic signs or symptoms, normal CSF and inflammatory markers

• Tick removal (tweezers or blunt curved forceps) leads to rapid recovery, within 24 hours typically

Botulism

• Infants age 6d to 12 months

• Infant botulism: spores ingested, germination occurs, and toxin causes symptoms. Lack of competitive intestinal flora allows spores to germinate in infants

• Foodborne botulism: actual toxin ingested

• Honey and corn syrup risk factor

• Breastfeeding appears protective, with decreased rates and diminished severity

• Toxin binds at presynaptic segment of the neuromuscular junction (SNARE/SNAP proteins) and prevents Ach from being released into the neuromuscular junction (somewhat like tick paralysis)

• Toxin used in Botox

• Autonomic symptoms as toxin binds preganglionic parasympathetic and sympathetic pathways (both mediated via acetylcholine)

• Weak cry, poor suck and feeding, descending weakness, constipation. Autonomic symptoms. Enlarged, sluggishly reactive pupils

• Avoid aminoglycosides

• Diagnosed via isolation of organism or toxin in stool. EMG shows decreased compound motor action potential amplitude

• Human botulism immunoglobulin (BIG) critical in reducing hospital stay, requirement/duration of mechanical ventilation

Periodic Paralyses

• Hypokalemic, hyperkalemic, and normokalemic forms

• Typically have family history

• Hypokalemic form most commonly due to mutation in dihydropyridine receptor in voltage sensitive Ca channel. Shift in potassium leads to inexcitable muscle cells

• Onset of symptoms often after high carb meal or vigorous exercise followed by rest 

• Cold, stress, menses, pregnancy can also provoke episodes

• Weakness begins in proximal legs and extends distally, then to upper extremities

• Swallowing/respiratory function rarely affected, normal cranial nerve function

• Tx: normalization of potassium level (recognizing total body potassium is actually normal)

• Acetazolamide used for prophylaxis